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Multiple Myeloma

Clinical Description

Multiple myeloma is a cancer of the plasma cell, a type of lymphocyte that produces antibodies, proteins that normally fight infections. These abnormal plasma cells proliferate and accumulate in the bone marrow, thereby interfering with normal bone marrow function. Furthermore, instead of producing normal, fully formed antibodies to fight infections like normal plasma cells do, these abnormal plasma cells secrete abnormally large amounts of a single type of protein (“monoclonal immunoglobulin”) derived from one cell population (“monoclonal”). The plasma cells continuously make these proteins. These proteins may directly harm the kidney, or deposit in the kidneys and cause kidney disease. The abnormal myeloma cells also produce chemicals that stimulate other cells to dissolve bone. This causes bones to develop “holes”, or lytic lesions. 

There are several types of myeloma. Most cases have multiple marrow sites and the term “multiple myeloma” is used. Solitary plasmacytoma is when only one site is evident, and extramedulluary myeloma is when tissues other than marrow are involved. Tumors of plasma cells are known as plasmacytomas. 

Symptoms of Multiple Myeloma

Since multiple myeloma often involves bone lesions, the most common early symptom of multiple myeloma is bone pain, which usually occurs in the lower back or ribs but may involve any bone. The bone lesions release calcium into the blood, and can cause high calcium levels. Since the abnormal plasma cells in multiple myeloma produce proteins in an uncontrolled manner which can cause kidney dysfunction, patients may experience symptoms of kidney failure, such as fatigue, decreased urination and swelling of the feet and legs. 

Since multiple myeloma involves abnormal plasma cells that accumulate and crowd out the normal marrow, patients may have a marrow that does not function properly. This leads to patients having low red blood cell levels (anemia), and low levels of white blood cells and platelets. As a result, patients can experience fatigue, weakness and shortness of breath on exertion due to anemia, infections due to low white blood cell counts, and easy bruising, or nose or gum bleeding due to low platelets (small cells that help blood to clot). 

Risk Factors of Multiple Myeloma

Myeloma rarely occurs in people younger than 40 yrs. Most cases occur after age 60. African-Americans have a higher rate of myeloma. Previous radiation and chemotherapy has not been shown to cause myeloma.
How Multiple Myeloma is Diagnosed.

Multiple myeloma can be diagnosed by examining the blood, urine and the bone marrow, and by X-rays of the skeleton. The diagnosis of multiple myeloma depends on finding increased bone marrow myeloma cells (malignant plasma cells) by bone marrow aspiration and biopsy, and either increased “monoclonal” proteins (“M” component) in the blood/urine, or bone lesions on X-ray. 

Other tests may aid as well. Blood cell counts are measured and may show low red blood, white blood and platelet cell counts, showing the degree which to bone marrow is affected. Calcium due to bone destruction can be high, and the protein albumin may be low. Beta-2 microglobulin is a protein that is an indirect measure of the size and growth rate of myeloma. Lastly, kidney function is determined by blood tests. 

Treatment Options for Multiple Myeloma at Tufts Medical Center

Patients should first be evaluated by a specialist to determine the stage of myeloma and the genes in the abnormal plasma cells. Some patients can have ‘smoldering’ myeloma – when the abnormal protein has been detected and there are more than 10% abnormal plasma cells in the bone marrow but there are no sympotms because there is no organ damage. Other patients can have “monoclonal gammopathy of undetermined significance” or MGUS when the abnormal protein is found but the percentage of abnormal plasma cell is less than 10%. 

For the majority of patients, myeloma cannot be cured but it can become a chronic treatable disease. The goal of treatment is to prolong survival and prevent organ damage, thereby alleviating symptoms. Therapy with combinations of several drugs – including the new drugs bortezomib and lenalidomide -- is the mainstay. Most patients, even when they are older (up to 75 years old), should be considered for an autologous stem cell transplant when the myeloma is at a minimal stage following initial therapy. The stem cells are collected from the patient by a process called leukapheresis and returned after a round of high dose chemotherapy. This treatment is generally well-tolerated and can keep the myeloma in a remission for a number of years when followed by consolidation and maintenance therapy. In some patients this transplant can be repeated when the disease comes back. 

When myeloma relapses, numerous standard and protocol based therapies are available at Tufts, including treatment with new monoclonal antibodies such as daratumumab and new agents such as selinexor. In addition, at Tufts an option for younger patients is to get a stem cell transplant from a sibling or unrelated donor.  

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Doctors + Care Team

Andreas K. Klein, MD

Andreas K. Klein, MD

Title(s): Associate Chief, Division of Hematology Oncology; Director, Hematologic Malignancies Program; Assistant Director, Bone Marrow and Hematopoietic Cell Transplant Program; Chair, Tufts Health Sciences Campus Institutional Review Boards; Associate Professor, Tufts University School of Medicine
Department(s): Medicine, Hematology/Oncology
Appt. Phone: 617-636-6227
Fax #: 617-636-8538

Lymphoma, myeloma, bone marrow transplantation (BMT), immune reconstitution after BMT

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Kellie A. Sprague, MD

Kellie A. Sprague, MD

Title(s): Director, Bone Marrow and Stem Cell Transplant Program; Director, Adult Leukemia Program; Assistant Professor, Tufts University School of Medicine
Department(s): Medicine, Hematology/Oncology
Appt. Phone: 617-636-6227
Fax #: 617-636-8538

Bone marrow transplantation, acute and chronic leukemia, myelodysplastic syndromes, lymphoma, myeloma, myeloproliferative disorders

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Kenneth B. Miller, MD

Kenneth B. Miller, MD

Title(s): Associate Chief, Division of Hematology/Oncology; Professor, Tufts University School of Medicine
Department(s): Medicine, Hematology/Oncology
Appt. Phone: 617-636-2600
Fax #: 866-322-3111

Acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), lymphoma, bone marrow and stem cell transplantation

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Monika Pilichowska, MD, PhD

Monika Pilichowska, MD, PhD

Title(s): Director, Hematopathology and Hematology Laboratory; Chair, Leadership Subcommittee, Women in Medicine and Science (WiMS); Associate Professor, Tufts University School of Medicine
Department(s): Pathology and Laboratory Medicine
Appt. Phone: 617-636-7216
Fax #: 617-636-7128

Hematology and hematopathology, flow cytometry, surgical pathology and cytology, renal pathology (medical renal disease)

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Raymond L. Comenzo, MD

Raymond L. Comenzo, MD

Title(s): Director, Transfusion Services; Director, John C. Davis Myeloma and Amyloid Program; Professor, Tufts University School of Medicine
Department(s): Medicine, Pathology and Laboratory Medicine, Hematology/Oncology
Appt. Phone: 617-636-6454
Fax #: 617-636-3175

Myeloma, amyloidosis, stem cell transplant, transfusion medicine

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Research + Clinical Trials

Characterization of T Cell Distribution in Stem Cell Mobilization

The purpose of this study is to collect blood samples from Tufts Medical Center multiple myeloma or AL amyloidosis patients being prepared for autologous stem cell transplant in order to analyze variations in T-cell populations through the stem cell mobilization process
More information about research and clinical trials

A Phase 2b, Open-Label, Single-Arm Study of Selinexor (KPT-330) Plus Low- Dose Dexamethasone (Sd) in Patients With Multiple Myeloma Previously Treated With Lenalidomide, Pomalidomide, Bortezomib, Carfilzomib, and an Anti-CD38 Monoclonal Antibody (mAb) and Refractory to Prior Treatment With Glucocorticoids, an Immunomodulatory Agent, a Proteasome Inhibitor and an Anti-CD38 mAb

This is a Phase 2b, single-arm, open-label, multicenter study of selinexor 80 mg plus dexamethasone 20 mg (Sd) dosed twice weekly in four-week cycles, in patients with penta-refractory MM (Parts 1 and 2) or quad refractory MM (Part 1 only).
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A Phase 3, Randomized, Placebo-Controlled, Double-Blind Study of Oral Ixazomib Maintenance Therapy After Initial Therapy in Patients With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation

This study will assess whether taking ixazomib as maintenance therapy after standard treatments extends the period of time that a patient’s cancer stays inactive.

Maintenance therapy means that a drug is taken for a relatively long period (in this study, up to 24 months) to prolong the time that the myeloma remains under control after a prior therapy; in this study the prior therapy must not include autologous stem cell transplant.  It is not yet proven whether maintenance therapy given to people with multiple meyloma is better than waiting until the myeloma comes back to receive additional treatment.  The study will assess whether taking ixazomib immediately after responding to a prior therapy allows people with multiple myeloma to live longer by preventing or delaying the return of their disease.

This study is also being performed for these additional research purposes:

  • To evaluate the safety of ixazomib and to learn about the side effects associated with the use of this drug when it is used as a maintenance therapy.
  • To find out whether the presence of certain genes and proteins in the cancer cells of patients with multiple myeloma can predict whether ixazomib will work on cancers similar to yours.
  • To evaluate the health and overall well-being of patients while they are taking ixazomib.

    More information about research and clinical trials

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